Biopsy pipettes are used in assisted reproduction techniques (ART) for the removal of blastomere(s) from embryos or polar bodies from oocytes, which may be done in order to perform preimplantation genetic diagnosis (PGD) on the genetic materials in the biopsied cell(s).

Device Description

The Biopsy pipette is part of the RI Pipettes range. Other pipettes available in this range include ICSI Injection, ICSI Holding, and Assisted Hatching pipettes.

Biopsy pipettes are offered in a range

ID sizes - 14μm, 20μm, 25μm, 30μm, 40μm .
bend angles 0°, 15°, 20°, 25°, 30°, 35°, 40°, 45° .
. tip profiles - flat , non-spiked (bevelled), spiked

All pipettes in this range are manufactured from very fine borosilicate glass, packed individually into a Twista-Pak (primary packaging) and sealed in a medical pouch. They are then batch sterilised by gamma irradiation.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:

Device: RI Pipettes - Biopsy

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Test)	Reported Device Performance
Non-pyrogenic (LAL)	< 20 EU/device
Non-embryotoxic (MEA)	≥ 80% blastocyst after 120h
Sterilization validation	Conforms to ISO 11137-1:2006 and ISO 11137-2:2007
Packaging validation	Conforms to ISO 11607-2:2006, ASTM F1980-07, ASTM F1886-09, ASTM F2054-13, and ASTM F1929-12
Shelf life	Device maintains specifications for the duration of its 3-year shelf life as demonstrated by real-time aging studies

2. Sample size used for the test set and data provenance:

Non-pyrogenic (LAL) and Non-embryotoxic (MEA): The document states "Each finished batch of pipettes is tested". This implies a continuous testing process rather than a single, fixed test set size. The specific number of pipettes tested per batch for these assays is not provided.
Data Provenance: The document does not explicitly state the country of origin for the data for these performance tests. Given that Research Instruments Ltd. is based in the UK, it's reasonable to infer the testing was conducted in the UK or by laboratories recognized by UK/EU standards, but this is not explicitly stated. The studies are prospective in the sense that they are routine batch release tests.
Sterilization, Packaging, and Shelf Life Validation: These are validation studies performed on representative samples, not on a batch-by-batch basis. The specific sample sizes for these validation studies are not provided in the document.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not applicable to the provided document. The performance tests described (LAL, MEA, sterilization, packaging, and shelf life) are objective laboratory and engineering tests, not subjective assessments requiring expert consensus.

4. Adjudication method for the test set:

This information is not applicable. The tests are objective and do not involve human adjudication in the way medical image analysis or clinical trials might. The acceptance criteria themselves serve as the 'adjudication' standard.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

This information is not applicable. This device is a microtool for assisted reproduction, not a diagnostic AI system or an imaging device that would typically involve human readers or AI assistance in interpretation.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

This information is not applicable. This device is a physical tool, not an algorithm.

7. The type of ground truth used:

Non-pyrogenic (LAL): The ground truth is established by a quantitative measure of endotoxin levels, with an objective threshold of "< 20 EU/device." This is a laboratory assay.
Non-embryotoxic (MEA): The ground truth is established by the survival and development rate of mouse embryos to blastocyst stage within a specified timeframe, with an objective threshold of "≥ 80% blastocyst after 120h." This is a biological assay.
Sterilization validation: The ground truth is compliance with international standards (ISO 11137-1:2006 and ISO 11137-2:2007) which dictate methods for achieving and verifying sterility assurance levels.
Packaging validation: The ground truth is compliance with international and ASTM standards (ISO 11607-2:2006, ASTM F1980-07, ASTM F1886-09, ASTM F2054-13, and ASTM F1929-12) which define performance requirements for sterile barrier systems.
Shelf life: The ground truth is the device maintaining its "specifications" (which would include the LAL, MEA, and physical characteristics) over time, as measured by real-time aging studies.

8. The sample size for the training set:

This information is not applicable. This device is a physical instrument, not a machine learning model that requires a training set. The descriptions relate to manufacturing and quality control processes.

9. How the ground truth for the training set was established:

This information is not applicable. As stated above, this device does not involve a training set.

Summary

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RESEARCH INSTRUMENTS LIMITED

Bickland Industrial Park, Faimouth, Cornwall, TR11 4TA, U.K. Tel: 01326 372753 [+44 1326 372 753] Fax: 01326 378783 [+44 1326 378 783] e-mail: sales@research-instruments.com www.research-instruments.com

510(k) Summary

Date prepared

Wednesday, 07 May 2014

Submitter

Company Name:	Research Instruments Ltd.
Registration Number:	9617095
Address:	Bickland Industrial Park
	Falmouth,
	Cornwall TR11 4TA
	United Kingdom
Telephone:	+44 (0) 1326 372 753
Fax:	+44 (0) 1326 378 783
Contact person:	David Lansdowne
Contact Title:	Technical Director
Contact email:	david@research-instruments.com

Device Name

Trade Name: RI Pipettes - Biopsy Common name: RI Pipettes Classification Name: Microtools, Assisted Reproduction (21CFR 884.6130, 85 MQH) Classification Panel: Obstetrics/Gynecology 510(K): K133257

Predicate Device

The RI Pipette - Biopsy claim substantial equivalence to two devices which have US market clearance.

Predicate 1

Trade Name:	RI Pipettes - ICSI Injection, Holding, Assisted Hatching, Denuding
Manufacturer:	Research Instruments Ltd
Classification Name:	Microtools, Assisted Reproduction
510(K):	K991261
Regulation Number:	21CFR 844.6130
Product Code:	MQH

Predicate 2

Trade Name:	Polar body biopsy micropipet and blastomere biopsy micropipet
Manufacturer:	Humagen Fertility Diagnostics, Inc
Classification Name:	Microtools, Assisted Reproduction
510(K):	K012811
Regulation Number:	21CFR 884.6130
Product Code:	MOH

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RESEARCH INSTRUMENTS LIMITED

Description of the Device

The Biopsy pipette is part of the RI Pipettes range. Other pipettes available in this range include ICSI Injection, ICSI Holding, and Assisted Hatching pipettes.

Biopsy pipettes are offered in a range

ID sizes - 14μm, 20μm, 25μm, 30μm, 40μm .
bend angles 0°, 15°, 20°, 25°, 30°, 35°, 40°, 45° .
. tip profiles - flat , non-spiked (bevelled), spiked

Summary of Performance Testing

Each finished batch of pipettes is tested to prove

. non-pyrogenic by Limulus Amoebocyte Lysate (LAL) per AAMI ST72:2002/(R)2010. Testing acceptance: < 20 EU/device
. non-embryotoxic by Mouse Embryo Assay (MEA) Testing acceptance: Pass level: ≥80% blastocyst after 120h

The sterilization process was validated per ISO 11137-1:2006 and ISO 11137-2:2007.

The packaging was validated per ISO 11607-2:2006, ASTM F1980-07, ASTM F1886-09, ASTM F2054-13, and ASTM F1929-12.

Results of real-time aging studies demonstrate the device maintains its specifications for the duration of its shelf life.

Indications for Use

Technological Characteristics

RI Pipette - Biopsy claims substantial equivalence to the

RI Pipettes range with respect to raw material, manufacturing process, packaging, sealing and 1. irradiation processes, pre-clinical testing and batch release criteria. The only difference between the RI Biopsy pipettes and the other pipettes in the RI range of pipettes is its intended use and tip geometry ie the size and profile of the tip is specific to the 'biopsy' intended use.
1. Humagen Pipettes with regard to raw material, manufacturing and irradiation processes and pre-clinical testing. The intended use is the same and tip geometry is also very similar. Any differences in geometry are the manufacturers' response to perceived user preference and do not affect the safety and effectiveness of the device when used as labelled. The RI Pipettes has a 3 year shelf life where the predicate device has a 2 year shelf life.

These differences do not affect the safety and effectiveness of the intended purpose.

Conclusion

The subject device is substantially equivalent to the predicate devices based on intended use, sterilization validation, and bench performance testing (MEA and LAL).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

May 16, 2014

Research Instruments Limited David Lansdowne Technical Director Bickland Industrial Park Falmouth, Cornwall TR114TA United Kingdom

Re: K133257

Trade/Device Name: RI Pipettes - Biopsy Regulation Number: 21 CFR§ 884.6130 Regulation Name: Assisted reproduction microtools Regulatory Class: II Product Code: MQH Dated: April 14, 2014 Received: April 14, 2014

Dear David Lansdowne,

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies.

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Page 2 - David Lansdowne

You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDeyices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Benjamin Fisher -S

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K133257

Device Name

RI Pipettes - Biopsy

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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Regulation Number and Section

§ 884.6130 Assisted reproduction microtools.

(a)
Identification. Assisted reproduction microtools are pipettes or other devices used in the laboratory to denude, micromanipulate, hold, or transfer human gametes or embryos for assisted hatching, intracytoplasmic sperm injection (ICSI), or other assisted reproduction methods.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when the assisted reproduction microtools (pipettes) are manufactured from glass, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.